Chemistry Reference
In-Depth Information
N
HCbz
CO
2
Me
OAc
O
50
AcO
AcO
S
CO
2
Me
NHCbz
AcHN
52
(89%)
OAc
O
max
365 nm
DPAP, CH
2
Cl
2
l
AcO
AcO
SH
AcHN
N
HFmoc
30 min
OAc
O
49
CO
2
t
-Bu
N
HFmoc
AcO
AcO
S
51
CO
2
t
-Bu
AcHN
53
(53%)
SCHEME 3.16
TEC-based synthesis of
S
-glycosyl amino acids.
integrity [37]. The scope of this approach was further demonstrated by the successful
coupling of alkenyl glycines
50
and
51
with peracetylated glucosyl and lactosyl thiols.
Synthesis of S-glycosyl amino acids
52
and
53
. DPAP (0.01 mmol) was added to a
solution of alkenyl glycines
50
or
51
(0.10 mmol) and glycosyl thiol
49
(0.12 mmol)
in CH
2
Cl
2
(1 mL). The solution was irradiated (
max
365 nm) at room temperature
for 30 minutes under magnetic stirring and then concentrated. The residue was eluted
from a column of silica gel (AcOEt-cyclohexane) to give the
S
-glycosyl amino acid
52
(89%), [
47.5 (
c
1.2, CHCl
3
).
Interestingly, one of the glycosyl amino acids thus obtained was used in the
assembly of an
S
-linked glycopeptide via solution phase chemistry (Scheme 3.17).
Succinctly, the
N
-protected glucosyl amino acid
54
was coupled with phenylalanine
ethyl ester under basic conditions and in the presence of a condensing agent to give the
N
-Fmoc-protected dipeptide
55
. This was liberated of the
N
-Fmoc protective group
by basic treatment and the free amine was condensed with
N
-Boc alanine under basic
conditions and in the presence of a condensing agent. The pure final tripeptide
56
featuring a pendant glucoside residue linked through a robust thioether linkage was
isolated by chromatography in 75% yield. Significantly, this compound turned out to
be a single diastereomer by NMR analysis, thus indicating that all stereocenters of
the reactants employed remained unaltered throughout the whole synthetic sequence.
]
D
=−
12.2 (
c
0.9, CHCl
3
), or
53
(53%), [
]
D
=−
H-Phe-OEt
OAc
OAc
OAc
N
HFmoc
O
O
O
AcO
AcO
AcO
AcO
S
S
S
AcO
AcO
CO
2
H
AcO
AcO
AcO
75%
82%
O
H
N
H
N
54
EtO
2
C
EtO
2
C
NHBoc
NHFmoc
N
H
O
O
Boc-Ala-OH
56
55
SCHEME 3.17
Assembly of a non-natural
S
-glycopeptide.
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